Question

Alexa is a 25 year old graduate student who arranged an urgent appointment with her primary care provider because her ‘vision is blurry’ in her left eye. She states that two days ago her vision changed. She compares her visual field to looking through a fogged up window. Her provider interprets this to mean she has a decrease in contrast and brightness. Eye examination reveals a marked reduction of visual acuity of her left eye. A swinging flashlight test reveals an afferent pupillary defect (Marcus Gunn pupil) of her left eye (i.e., paradoxical papillary dilatation in response to increased light). Visual acuity and pupillary responses in her right eye are normal. Assessment of the retina and retinal vessels in both eyes is normal. Additional findings show patchy but consistent hypoesthesia (decreased feeling) to pin and light touch over her right limbs. On questioning, Alexia states that she experienced a self-limiting episode of numbness and tingling a few months ago. She also states that she has been experiencing fatigue, particularly at the end of the day. She denies depression, and her family history is unrevealing. The remainder of the physical exam in normal. Alexa is referred to an ophthalmologist who diagnoses optic neuritis (inflammation of the optic nerve). She begins corticosteroid treatment, and is referred to a neurologist who schedules a cranial MRI with gadolinium. The MRI reveals the presence of multiple deep white matter lesions scattered throughout the brain, suggesting multiple sclerosis. A subsequent lumbar puncture and analysis of Alexia’s cerebral spinal fluid (CSF) is consistent with possible multiple sclerosis. Further work-up rules out other possible causes. Ultimately, the neurologist diagnoses Alexia with relapsing-remitting multiple sclerosis.

1. What immune mechanisms contribute to the pathophysiology of multiple sclerosis? In your answer, discuss the subsets of lymphocytes involved and their role in the autoimmune process. Discuss the type and role of cytokines in the autoimmune process underlying multiple sclerosis.

Answer 1

Multiple sclerosis is autoimmune disorder of central nervous system(CNS) sparing peripheral nervous system and not much systemic involvement .

In MS there is inflammation of axons leading to demyelination further causing gliosis ( scarring ) and axonal destruction, neuronal loss ,eventually cortical atrophy .

Inflammatiom + Demyelination Of CNS = MS

Pathophysiology -
Inflammation activate B cell and T cell
B cell forms antibodies against
1) MBP (Myelin Base Protein )
2) MOGP ( Myelin oligodendrocyte glycoprotein )

T cells - Perivenular cuffing affecting white matter and disrupts Blood brain barrier (BBB) and cause demyelination .
Further due to demyelination saltatory conduction is lost .

Role of Cytokines

T-helper type 1 (TH1) cells producing interferon γ (IFN-γ) .Proinflammatory TH17 cells are induced by transforming growth factor β (TGF-β) and IL-6 and are amplified by IL-21 and IL-23. TH17 cells and its cytokine IL-17 are increased in MS lesions. TH1 cytokines, including IL-2, tumor necrosis factor (TNF)-α, and IFN-γ, help in activating and maintaining autoimmune responses TNF-α and IFN-γ may directly injured oligodendrocytes or the myelin membrane.